The long-term goal of this research is to understand the neural and chemical mechanisms that generate the different states of the brain and organism: waking (W), slow wave sleep (SWS) and paradoxical sleep (PS or rapid eye movement sleep, REM). During these states, the activity of the cerebral cortex undergoes fundamental changes, which are importantly determined by modulatory inputs from the basal forebrain. In human disease, lesions in this area can result in deficits in cortical activation and arousal, yet also in SWS. The aim of the proposed research is to identify by their neurotransmitters, including acetylcholine (ACh), GABA and glutamate, those basal forebrain neurons which are responsible for cortical activation that occurs during W and PS, and those which are reciprocally responsible for the cortical de-activation that occurs during SWS. Moreover, whether basal forebrain neurons, including cholinergic, GABAergic and glutamatergic cells, modulate cortical activity in a rhythmic manner will be tested according to the thesis that such rhythmic modulation may provide a mechanism for integrated coherent activity across cortical networks during cortical activation. In unanesthetized, head-restrained rats neurons will be recorded by extracellular technique to be characterized according to their discharge properties in relation to the cortical electroencephalogram (EEG) during the natural states of W, SWS and PS. The electrophysiologically characterized neurons will be labeled with neurobiotin by the juxtacellular technique, revealed as cholinergic, GABAergic or glutamatergic using triple fluorescent staining and delineated according to their somatodendritic morphology and axonal projections. These studies will identify for the first time the specific neurons that are critically involved in state determination and reveal the discharge, chemical neurotransmitters and efferent projections by which they modulate cerebral activity across the sleep-wake cycle [unreadable] [unreadable]